(2,3-Z)-4-(3-methoxycarbonyl-2-quinolin-3-yl-allyl)piperidine-1-carboxylic acid tert-butyl ester | 1014679-77-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (2,3-Z)-4-(3-methoxycarbonyl-2-quinolin-3-yl-allyl)piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: 4-(3-methoxycarbonyl-2-quinolin-3-ylallyl)piperidine-1-carboxylic acid tert-butyl ester；tert-butyl 4-[(Z)-4-methoxy-4-oxo-2-quinolin-3-ylbut-2-enyl]piperidine-1-carboxylate
• CAS: 1014679-77-6
• 化学式: C₂₄H₃₀N₂O₄
• 分子量: 410.513
• InChiKey: IBMAVLMRHYCEIR-CYVLTUHYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  68.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2,3-Z)-4-(3-methoxycarbonyl-2-quinolin-3-yl-allyl)piperidine-1-carboxylic acid tert-butyl ester 在 Stryker's reagent polymethylhydrosiloxane 、 正丁醇 作用下， 以 甲苯 为溶剂， 以60%的产率得到(S)-4-(3-methoxycarbonyl-2-quinolin-3-yl-propyl)piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Suzuki−Miyaura Approach to JNJ-26076713, an Orally Active Tetrahydroquinoline-Containing α_Vβ₃/α_Vβ₅ Integrin Antagonist. Enantioselective Synthesis and Stereochemical Studies

  摘要：

  An improved scale-up synthesis was required for the alpha(V)beta(3)/alpha(V)beta(5) integrin antagonist 1, which had demonstrated oral efficacy in eye disease models of angiogenesis and vascular permeability. A stereodefined, quinoline-substituted, unsaturated ester was conveniently prepared by a Suzuki-Miyaura coupling to facilitate exploration of multiple methods of asymmetric reduction. The catalytic chiral hydrogenation of the corresponding unsaturated acid (Z-5b) with a ruthenium-based metal precursor and the (R)-XylPhanePhos ligand proved particularly efficient and economical. The resulting (3S)-quinoline-containing intermediate was reduced to an equal mixture of tetrahydroquinoline diastereomers. The undesired diastereomer could be recycled to the desired one by an oxidation/reduction protocol. The absolute stereochemistry of 1 was established as 3S,3'S by a combination of X-ray diffraction and chemical means.

  DOI：

  10.1021/jo702551t
• 作为产物：
  描述：

  4-(3-methoxycarbonyl-2-trifluoromethanesulfonyloxyallyl)piperidine-1-carboxylic acid tert-butyl ester 、 喹啉-3-硼酸 在 bis-triphenylphosphine-palladium(II) chloride sodium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 7.0h， 以67%的产率得到(2,3-Z)-4-(3-methoxycarbonyl-2-quinolin-3-yl-allyl)piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Enantioselective process for preparing a substituted alkanoic acid

  摘要：

  本发明涉及一种用于对手性选择性地制备替代哌啶烷基酸整合素拮抗剂化合物的方法。

  公开号：

  US20090124804A1

文献信息

• [EN] PIPERIDINYL COMPOUNDS THAT SELECTIVELY BIND INTEGRINS<br/>[FR] COMPOSES DE PIPERIDINYLE LIANT SELECTIVEMENT LES INTEGRINES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2004020435A1

  公开（公告）日：2004-03-11

  The invention is directed to piperidinyl compounds of formula (I) and (II) that selectively bind integrin receptors and methods for treating an integrin mediated disorder, wherein W, R2, Z and q are described in the application.

  这项发明涉及选择性结合整合素受体的式(I)和(II)的哌啶基化合物，以及治疗整合素介导的疾病的方法，其中W、R2、Z和q在申请中有描述。
• [EN] ENANTIOSELECTIVE PROCESS FOR PREPARING A SUBSTITUTED ALKANOIC ACID<br/>[FR] PROCÉDÉ ÉNANTIOSÉLECTIF POUR PRÉPARER UN ACIDE ALCANOÏQUE SUBSTITUÉ
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2009058314A1

  公开（公告）日：2009-05-07

  The present invention is directed to a process for enantioselectively preparing substituted piperidine alkanoic acid integrin antagonist compounds.

  本发明涉及一种手性选择性制备取代哌啶烷基酸整合素拮抗剂化合物的方法。
• Piperidinyl compounds that selectively bind integrins
  申请人：De Corte Bart

  公开号：US20080058359A1

  公开（公告）日：2008-03-06

  The invention is directed to piperidinyl compounds that selectively bind integrin receptors and methods for treating an integrin mediated disorder.

  这项发明涉及选择性结合整合素受体的哌啶化合物以及治疗整合素介导疾病的方法。
• PIPERIDINYL COMPOUNDS THAT SELECTIVELY BIND INTEGRINS
  申请人：De Corte Bart

  公开号：US20110092528A1

  公开（公告）日：2011-04-21

  The invention is directed to piperidinyl compounds that selectively bind integrin receptors and methods for treating an integrin mediated disorder.

  本发明涉及选择性结合整合素受体的哌啶化合物和治疗整合素介导的疾病的方法。
• Synthesis of an αvβ3 integrin antagonist intermediate via asymmetric hydrogenation of an α,β-unsaturated ester with BoPhoz-iridium and BoPhoz-rhodium catalysts
  作者：Antonio Zanotti-Gerosa、William A. Kinney、Gabriela A. Grasa、Jonathan Medlock、Andreas Seger、Shyamali Ghosh、Christopher A. Teleha、Bruce E. Maryanoff

  DOI：10.1016/j.tetasy.2008.03.031

  日期：2008.5

  The enantioselective synthesis of an alpha(v)beta(3) integrin antagonist intermediate was approached via asymmetric hydrogenation of a beta,beta-disubstituted-alpha,beta-unsaturated ester. As a result of the rapid parallel screening of a selection of ligands and catalysts, we found that neutral Me-BoPhoz-rhodium and iridium catalysts effect the required transformation with a high enantioselectivity. Both the activity and selectivity of the catalysts were strongly dependent on the choice of solvent and counter-ion. The addition of iodine modified the iridium catalyst such that the reduction of the 3-substituted quinoline ring took place. (C) 2008 Elsevier Ltd. All rights reserved.